Lung fluid balance is influenced by changes in the structure of the microvascular barrier. Our objective is to develop a new optical method for measuring lung filtration coefficient (K-fc). The method does not use radioactive tracers and, once verified, could be used in intact animals and humans to monitor fluid exchange and assess the efficacy of therapy. The method is based on a simple dilution principle. Intravascular proteins are labeled with Evans blue and a change in microvascular pressure is transmitted to the lung. Since water moves more easily through the microvascular barrier than protein, there will be a slight increase in protein concentration at the outlet of the lung following a pressure elevation. This can be measured optically, and transvascular filtration rate determined by the application of conservation of mass and the Starling Equation. We have tested the theory in hollow fiber systems and found it to provide an accurate measure of fluid filtration when compared either to direct filtration measurement, or to measured weight changes. However, artifacts caused by high red cell absorbance had limited its application in isolated lung studies to cases where hematocrit and flow were low. Under these circumstances, K-fc determined optically is consistently lower than estimates based on the weight.change method. We have found that the difference agrees with an independent measure of blood volume accumulation, indicating that the optical method is more accurate than gravimetric measures since it is independent of changes in vascular volume. We have eliminated red cell artifacts by first passing blood through polysulfone fibers before measuring optical absorbance. Suitable fibers have been developed for these studies by chemists at the Research Division of W. R. Grace, Inc. We propose here to test the sensitivity of the optical method to changes in lung vascular surface area, permeability, blood flow, and pressure step size. A more sensitive optical system than the one we now use gas been designed and a prototype tested. The prototype can detect 0.05% changes in protein concentration, sensitive enough for human studies. The system has been tested in isolated dog lungs and was used to measure transvascular fluid exchange in an intact sheep under normal physiological conditions. Theme optical measurements are the first non-gravimetric, non-lymph measurements of lung microvascular filtration in live animals, and demonstrate the feasibility of using this technique to study lung physiology and pathophysiology without the need to correct for vascular volume changes.